Synthesis and Acetylcholinesterase Inhibitory Activity of 6-Benzyl-3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one Derivatives
ZHAO Yang1, HOU Jian1, ZHANG Qing-guang1, JIN Zhe1, LI Xue-song1, LIU Xiao-ping1*, WAN David Chicheong2, HU Chun1*
1. Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China; 2. School of Biomedical Sciences, The Chinese University of Hongkong, Hongkong 999077, China
Abstract��OBJECTIVE To explore the synthesis and acetylcholinesterase inhibitory activity of 6-benzyl-3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives. METHODS Benzaldehyde and acetylglycine were used as raw materials and underwent Erlenmeyer-Pl��chl reaction, condensation reaction, hydrolysis reaction, condensation reaction to obtain 6-benzyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-ones derivatives. The derivatives reacted with substituted ��-phenacyl chlorides to generate 6-benzyl-3-(hydroxylaryl)-7H-thiazolo[3,2-b]-1,2,4-triazin-7-ones derivatives. Then, Williamson reaction was used to yield 6-benzyl-3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-ones as target compounds. RESULTS Nine 6-benzyl-3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-ones were prepared as target compounds. All target compounds exhibited inhibitory activities against human AChE in vitro, five of which had inhibitory rates above 50% at 10 ��mol��L-1. CONCLUSION Based on the screening results of AChE inhibitory activity in vitro and docking studies, there are some interactions between 6-benzyl-3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives and the anionic binding site and PAS zones of AChE, and the target compounds have exhibited AChE inhibitory activities.
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ZHAO Yang, HOU Jian, ZHANG Qing-guang, JIN Zhe, LI Xue-song, LIU Xiao-ping, WAN David Chicheong, HU Chun. Synthesis and Acetylcholinesterase Inhibitory Activity of 6-Benzyl-3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one Derivatives. Chinese Pharmaceutical Journal, 2018, 53(8): 579-584.
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2018, Vol. 53 
